Effective bio-targeting luminescent nanoparticles must be non-toxic, small relative to the system they are imaging, stable over the course of the experiment, and able to target the desired entity. Semiconductor quantum dots have received considerable attention for biological applications such as cellular imaging, but have significant drawbacks, including constituent toxic elements (e.g., CdSe), need for UV excitation which can limit their use in vitro and compromise in vivo applications, difficulty to meet narrow particle size requirements, and requirement for extensive surface modification both to prevent ion loss and to bond appropriate bio-receptor molecules.
Untreated nanocrystals present drawbacks for use as biomolecular probes. Such particles tend to aggregate, and lack surface groups that can be used to attach biomolecular probes. While surface coating with silica/siloxane layers is a common method of enabling particle-biomolecule conjugation, this treatment can significantly increase particle size, which affects transport to and into cells, and silica and siloxane coatings can be hydrolytically unstable under physiological conditions.
Other nanoparticles such as rare earth ion-doped yttrium oxide (Y2O3) are attractive targeting agents for several significant reasons: they are benign in vitro and in vivo and can be made with diameters<20 nm. They can be synthesized to have strong emission in the UV, visible, or IR by varying lanthanide dopant ions (so narrow particle size distributions are not necessary), and can be doped for down- or up-conversion emission. Yet, rare earth ion-doped Y2O3 nanoparticles have seen only limited use for targeting biological systems. Techniques that would enable yttria nanoparticles to satisfy the requirements for targeting agents have heretofore been unattainable.
Hence, there exists a need for robust nanoparticles and methods of making same functionalized for bonding to biomolecules.